In general, in a qualitative analysis using a mass spectrometer, the mass-to-charge ratio of a peak appearing on a mass spectrum obtained in actual measurement on a sample is compared with a molecular weight obtained from a composition formula of a known compound, whereby it is determined whether or not the compound is contained in the sample. Further, in an analysis using a mass spectrometer with high mass resolution and high mass accuracy, such as a time-of-flight mass spectrometer (hereinafter, abbreviated as “TOFMS”), the mass-to-charge ratio of a peak appearing on a mass spectrum obtained in actual measurement is compared with the monoisotopic mass of a compound, whereby the structure of the compound can be estimated. Still further, the intensity pattern of an isotope peak appearing on a mass spectrum is used to estimate the structure of a compound. Still further, in an analysis using an MSn mass spectrometer, a target ion is dissociated one or more times, the generated ions are subjected to mass analysis to obtain an MSn spectrum, and the mass-to-charge ratio and the intensity pattern of a peak on the MSn spectrum thus obtained are used to analyze the structure of a compound with a high molecular weight, such as proteins and peptides.
In the case where a high-concentration sample is measured using a mass spectrometer, particularly, a mass spectrometer with high mass resolution and high mass accuracy, a signal may be saturated in a detector, or an input signal may fall outside of the input range of an analog/digital converter, a time/digital converter, and the like which convert a detection signal from the detector into a digital value, with the result that the peak intensity may be saturated on a mass spectrum. If such saturation of the peak intensity occurs, the accuracy of mass calculated from the barycentric position or the like of the peak waveform may become lower, and the reproducibility of an isotope peak pattern appearing on the mass spectrum may become lower.
The upper graph of FIG. 3 is a chromatogram (total ion chromatogram) acquired by a conventional liquid chromatograph mass spectrometer (LC/MS), and the lower two graphs of FIG. 3 are mass spectra at a time point t1 and a time point t2 within the time range of one peak originating from the same component in the chromatogram above. In the mass spectrum at the time point t1 near a peak top on the chromatogram, a peak P1 originating from the target component is saturated. In such a state, a mass-to-charge ratio M1 calculated from the peak P1 is unfavorably different from a mass-to-charge ratio M2 calculated from a peak P2 on the mass spectrum at the time point t2 at which saturation does not occur. If such a decrease in mass accuracy occurs, compound identification based on a mass spectrum becomes difficult, or incorrect identification may occur.
The most common method for avoiding such a trouble during measurement of a high-concentration sample as described above involves diluting the sample or adjusting the sample introduction amount, and measuring the sample again. Unfortunately, this method cannot be adopted in the case where the sample is not left for the remeasurement, and is not suitable for the case where the sample is very precious and expensive.
Non-Patent Document 1 discloses the following method. In an ion trap time-of-flight mass spectrometer, in the case where the concentration of a sample is high, the ion storage time at an ion trap is shortened, and the amount of ions used for mass spectrometry is thus reduced, whereby saturation of a peak intensity is avoided. Further, Patent Document 1 discloses the following method. In a MALDI time-of-flight mass spectrometer, in the case where excessive generation of ions is detected on the basis of a change in potential of a sample plate, a lens voltage is controlled such that the ion pass efficiency of an ion lens decreases, and the amount of ions used for mass spectrometry is thus reduced, whereby saturation of a peak intensity is avoided.
As described above, the methods for reducing the amount of ions used for mass spectrometry are effective to avoid saturation of a peak intensity. However, for example, according to the former method, the sensitivity to all ions that are stored in the ion trap in one cycle decreases. Hence, in the case where a low-concentration component exists on a chromatogram at a position temporally close to a high-concentration component, the sensitivity to the low-concentration component also decreases, and the low-concentration component may not be detected. Similarly, according to the latter method, the sensitivity to other ions that pass through the ion lens before and after ions corresponding to a particular high-concentration component pass through the ion lens inevitably decreases, so that the other ions may not be detected. Further, in both the methods, if an optimal control should be performed taking various elements such as the kind of analysis target sample and measurement conditions into consideration, the control should be unfavorably complicated.
In a qualitative analysis using a LC/MS or a GC/MS including a quadrupole mass spectrometer with a quadrupole mass filter, the quadrupole mass spectrometer performs scan measurement, and a mass spectrum over a predetermined mass-to-charge ratio range is repetitively acquired. The patterns of the mass spectra are compared with mass spectrum patterns stored in a spectrum database (library). Thus, a compound having a high degree of similarity in pattern is extracted, and a compound corresponding to a peak on a chromatogram is identified. In the case where a sharp peak having a small temporal width appears on the chromatogram, a qualitative analysis may be performed using a mass spectrum at a measurement point (measurement time point) giving the top of the sharp peak.
A peak on a chromatogram is in many cases made less sharp or deformed by various factors, and hence it is difficult to strictly determine a measurement point giving a peak top. In preparation for such a case, a conventional data processing apparatus for a GC/MS or a LC/MS has a function of calculating an average mass spectrum obtained by averaging mass spectra at a plurality of measurement points (generally, about three to five points) near a peak top on a chromatogram (see Non-Patent Document 2).
In a GC/MS/MS or a LC/MS/MS including a tandem quadrupole mass spectrometer as a mass spectrometer, an analysis in a multiple reaction monitoring (MRM) measurement mode is frequently adopted for a quantitative analysis of a target compound. In the MRM measurement mode, an upstream quadrupole mass filter and a downstream quadrupole mass filter each allow only ions having a particular mass-to-charge ratio to pass therethrough, and ions that finally reach a detector are detected. The MRM measurement mode has an advantage that ions originating from a non-target component and ions originating from a target component, which cannot be separated by a chromatograph, can be separated from each other and that only the latter ions can be detected. In the MRM measurement mode, however, qualitative information cannot be obtained in a period other than retention time, and hence, even if an unknown component is contained in a sample, the component is difficult to identify.
In view of the above, in a conventional GC/MS/MS or LC/MS/MS, MRM measurement and scan measurement are alternately repeated at a time interval that is short enough to be regarded as practically the same time, whereby quantitative information obtained in the MRM measurement and qualitative information obtained in the scan measurement can be acquired in parallel. Unfortunately, the following problem arises in the case where the MRM measurement and the scan measurement are alternately repeated at such a short time interval.
That is, in the MRM measurement, ion selection is achieved by the quadrupole mass filters at two stages, and hence the amount of ions that reach the detector is significantly smaller than that in the simple scan measurement in which ions simply pass through one of the quadrupole mass filters. Meanwhile, the MRM measurement in which a quantitative analysis is performed requires a high sensitivity. Accordingly, in general, in the case where the MRM measurement and the scan measurement are carried out at the same time (which is actually time-sharing as described above in a strict sense, but can be regarded as practically the same time in a longer time period), the gain of the detector is set to be high enough to obtain sufficient detection signals even with a relatively small amount of ions obtained in the MRM measurement. However, if the gain of the detector is high as described above, detection signals obtained in the scan measurement exceed the input range of an A/D converter, so that saturation of data frequently occurs.
If signal intensity data at a given mass-to-charge ratio is saturated in the scan measurement, the pattern of a mass spectrum at this time loses its shape (see FIGS. 3). When an average mass spectrum is calculated as described above in a predetermined time range near a peak top on a chromatogram, if mass spectra used for this average calculation include such a mass spectrum whose pattern loses its shape, the resultant average mass spectrum may not properly represent characteristics of a target compound. In this case, an incorrect compound may be selected in database searching, resulting in incorrect identification. Otherwise, a correct compound may not be selected in database searching, resulting in an identification miss.